Shujie Li,1,* Baiyi Yi,1,* Huan Wang,2 Xianghuai Xu,1 Li Yu1 

1Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Clinical Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xianghuai Xu, Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, People’s Republic of China, Email 05849@tongji.edu.cn Li Yu, Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, No. 389 Xincun Road, Shanghai, 200065, People’s Republic of China, Email 96778@tongji.edu.cn

Purpose: This study aims to comparatively evaluate the efficacy and safety profiles of biologic agents targeting type 2 inflammation in COPD.
Methods: As of September 1, 2024, we identified and screened eight clinical studies evaluating biologic agents targeting type 2 inflammation for COPD treatment from multiple databases. Following data extraction, we conducted a network meta-analysis using R software to indirectly compare the efficacy and safety profiles of the five included biologic agents, incorporating visualization of the analytical results.
Results: In COPD patients with elevated eosinophil levels (peripheral blood eosinophil count ≥ 200 cells/μL), dupilumab demonstrated significant therapeutic efficacy by: (1) reducing the annualized rate of acute exacerbations (versus placebo: − 0.44; 95% CI − 0.77 to − 0.10), (2) decreasing SGRQ total scores (versus placebo: − 3.41; 95% CI − 6.00 to − 0.82), and (3) increasing pre-bronchodilator FEV1 (versus placebo: 0.06 L; 95% CI 0.00 to 0.12). Benralizumab also showed clinical benefits in reducing acute exacerbation rates (10 mg versus placebo: − 0.21; 95% CI − 0.39 to − 0.04) and improving SGRQ scores (100 mg versus placebo: − 1.70; 95% CI − 3.35 to − 0.04). Furthermore, all five biologic agents evaluated in this network meta-analysis exhibited favorable safety profiles.
Conclusion: This NMA demonstrates that both dupilumab and benralizumab show statistically significant efficacy in COPD management, particularly among patients with eosinophilic inflammation. And these biological agents maintain favorable safety profiles. Future research should focus on large-scale multicenter clinical trials, biomarker-based patient stratification, optimization of drug delivery regimens, and development of multi-target combination therapies.
Plain Language Summary: Biological therapy represents an emerging treatment approach for COPD, with several biological agents under development, including benralizumab, mepolizumab, itepekimab, astegolimab, and dupilumab. Which of these biological agents demonstrates optimal efficacy? Which exhibits the most favorable safety profile? These critical questions form the focus of the present investigation. In the absence of direct comparative clinical trials evaluating these biological agents, we employed network meta-analysis to estimate their relative efficacy and safety. Our analysis ultimately demonstrated that among the five biological agents targeting type 2 inflammation in COPD, only dupilumab and benralizumab exhibited significant therapeutic efficacy, particularly in patient populations with elevated eosinophil levels. Furthermore, all investigated biological agents demonstrated favorable safety profiles. This finding not only addresses the current lack of direct comparative evidence, but also indicates that patients with elevated eosinophil levels may represent the optimal target population for biological therapy.

Keywords: COPD, biologics, type 2 inflammation, network meta-analysis